Department of Endocrinology, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK.
Clin Endocrinol (Oxf). 2020 Nov;93(5):528-538. doi: 10.1111/cen.14289. Epub 2020 Aug 14.
The citric acid cycle, also known as the Krebs cycle, plays an integral role in cellular metabolism and aerobic respiration. Mutations in genes encoding the citric acid cycle enzymes succinate dehydrogenase, fumarate hydratase and malate dehydrogenase all predispose to hereditary tumour syndromes. The succinate dehydrogenase enzyme complex (SDH) couples the oxidation of succinate to fumarate in the citric acid cycle and the reduction of ubiquinone to ubiquinol in the electron transport chain. A loss of function in the succinate dehydrogenase (SDH) enzyme complex is most commonly caused by an inherited mutation in one of the four SDHx genes (SDHA, SDHB, SDHC and SDHD). This mechanism was first implicated in familial phaeochromocytoma and paraganglioma. However, over the past two decades the spectrum of tumours associated with SDH deficiency has been extended to include gastrointestinal stromal tumours (GIST), renal cell carcinoma (RCC) and pituitary adenomas. The aim of this review is to describe the extended tumour spectrum associated with SDHx gene mutations and to consider how functional tests may help to establish the role of SDHx mutations in new or unexpected tumour phenotypes.
柠檬酸循环，又称三羧酸循环，在细胞代谢和需氧呼吸中起着不可或缺的作用。编码柠檬酸循环酶琥珀酸脱氢酶、延胡索酸水合酶和苹果酸脱氢酶的基因突变都易导致遗传性肿瘤综合征。琥珀酸脱氢酶酶复合物（SDH）将琥珀酸的氧化与柠檬酸循环中的富马酸以及电子传递链中的泛醌与泛醇的还原偶联。琥珀酸脱氢酶（SDH）酶复合物的功能丧失最常见于四个 SDHx 基因（SDHA、SDHB、SDHC 和 SDHD）之一的遗传突变引起。该机制最初与家族性嗜铬细胞瘤和副神经节瘤有关。然而，在过去的二十年中，与 SDH 缺陷相关的肿瘤谱已扩展到包括胃肠道间质瘤（GIST）、肾细胞癌（RCC）和垂体腺瘤。本综述的目的是描述与 SDHx 基因突变相关的扩展的肿瘤谱，并探讨功能测试如何有助于确定 SDHx 突变在新的或意外的肿瘤表型中的作用。
